Murad, M. Hassan

Background and Aims: Endoscopic retrograde cholangiopancreatography (ERCP), percutaneous transhepatic biliary drainage, and endoscopic ultrasound (EUS)-guided biliary drainage are all established techniques for drainage of malignant biliary obstruction. This network meta-analysis (NMA) was aimed at comparing all 3 modalities to each other. Materials and Methods: Multiple databases were searched from inception to October 2019 to identify relevant studies. All the patients were eligible to receive any one of the 3 interventions. Data extraction and risk of bias assessment was performed using standardized tools. Outcomes of interest were technical success, clinical success, adverse events, and reintervention. Direct meta-analyses were performed using the random-effects model. NMA was conducted using a multivariate, consistency model with random-effects meta-regression. The GRADE approach was followed to rate the certainty of evidence. Results: The final analysis included 17 studies with 1566 patients. Direct meta-analysis suggested that EUS-guided biliary drainage had a lower reintervention rate than ERCP. NMA did not show statistically significant differences to favor any one intervention with certainty across all the outcomes. The overall certainty of evidence was found to be low to very low for all the outcomes. Conclusions: The available evidence did not favor any intervention for drainage of malignant biliary obstruction across all the outcomes assessed. ERCP with or without EUS should be considered first to allow simultaneous tissue acquisition and biliary drainage.

AbstractObjectiveTo describe the presentation and outcomes of patients with adrenal ganglioneuromas (AGNs).DesignSingle‐centre retrospective cohort study (1 January 1995 to 31 December 2019) and systematic review of literature (1 January 1980 to 19 November 2019).PatientsDiagnosed with histologically confirmed AGN.MeasurementsBaseline clinical, imaging and biochemical characteristics, recurrence rates and mortality. Subgroup analysis was performed on tumours with histologic elements of ganglioneuroma and pheochromocytoma (ie composite tumours).ResultsThe cohort study included 45 patients with AGN, 20 (44%) of which had composite tumours. Compared to pure AGN, patients with composite tumour were older (median age, 62.5 vs. 35 years, p < .001), had smaller tumours (median size, 3.9 vs. 5.7 cm, p = .016) and were discovered incidentally less frequently (65% vs. 84%, p = .009). No recurrences or ganglioneuroma‐specific mortality occurred during follow‐up (range, 0–266 months). The systematic review included 14 additional studies and 421 patients. The mean age of diagnosis was 39 years, and 47% were women. AGNs were discovered incidentally in 72% of patients, were predominantly unilateral (99%) and had a mean diameter of 5.8 cm and an unenhanced computed tomography (CT) attenuation of −118 to 49 Hounsfield units (HU). On imaging, 69% of AGNs were homogenous, 41% demonstrated calcifications, and 40% were lobulated.ConclusionsAGNs are rare benign tumours that present with variable imaging features including large size, unenhanced CT attenuation >20 HU, calcifications and lobulated shape. Imaging characteristics can assist in establishing a diagnosis and avoiding an unnecessary adrenalectomy. The association of pheochromocytomas with AGNs is frequent. Diagnosis should include biochemical testing.

Abstract Lifestyle interventions are pivotal for successful management of type 2 diabetes (T2D), however, the proportion of people with T2D adhering to physical activity advice has not been thoroughly studied. The purpose of this systematic review was to summarise the evidence on adherence to exercise or physical activity components in lifestyle interventions in those with T2D. We searched MEDLINE EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews and Scopus on 12 November 2019. Eligible studies enrolled adults with T2D and reported the proportion of adherence to lifestyle interventions as a primary or secondary outcome. We included 11 studies (nine randomised controlled trials (RCTs) enrolling 1717 patients and two nonrandomised studies enrolling 62 patients). Only one of the studies had low risk of bias. The proportion of participants adhering to physical activity varied from 32% to 100% with a median of 58%. Adherence was higher in interventions using supervised training and lowest in interventions using remote coaching and the adherence rate in observational studies was higher compared to RCTs (92% vs. 55%; p < 0.01). Study duration, risk of bias, or participants' sex, were not associated with adherence to physical activity. The proportion of those with T2D adhering to physical activity interventions for T2D varies widely and most of the included studies had a high risk of bias. These findings have important implications for planning and power analysis of future trials and when counselling patients about lifestyle interventions including physical activity or exercise components.

335 Background: Systematic reviews are outdated quickly when the evidence is rapidly evolving as the process is laborious and there is little incentive for primary author team of an index SRMA to update the evidence. Consequently, there is an epidemic of redundant SRMAs performed by different teams—sometimes with conflicted results—for treatment of first line mRCC. Methods: We have created a living, interactive systematic review (LISR)and network meta-analysis(LINMA) for the treatment of first line mRCC using an Artificial intelligence (AI) assisted framework for evidence synthesis (Living, Interactive evidence synthesis framework) (LIvE) . The framework is implemented in five-layered architecture (application layer, shared module layer, core service layer, middleware layer, and storage layer) which work together to automate the identification of new studies and analysis and semi-automate the screening and data extraction. Dynamic features such as interactive tables, figures and evidence maps are enabled using Python and JavaScript programming languages. Results: We have maintained a living, interactive evidence profile for the first line treatment mRCC since September 2019 ( LIVING WEBSITE) . Living search strategy identifies new studies as they become available. As of October 13, 2020 LISR, includes data 14 clinical trials ( PRISMA ). Baseline characteristics are summarized in an interactive table ( TABLE) . Cabozantinib& Nivolumab (Cabo-Nivo) is the highest ranked drug for improving Overall Response (OR), Progression Free Survival (PFS) and Overall Survival (OS) whereas Ipilimumab in combination with Nivolumab (Ipi-Nivo) is highest ranked drug for achieving complete response (CR). Ipi-Nivo and Atezolizumab & Bevacizumab (Ate-Bev) ranked highest and Cabo-Nivo ranked lowest for treatment related Adverse events (TRAEs). Results of network meta-analysis are summarized as interactive tables and plots ( NMA ), summary of findings tables ( MULTIPLE COMAPRISONS ) and evidence maps ( MAP ). Conclusions: LISRs can potentially reduce redundancy, increase transparency, reproducibility, enable shared-decision making (at a guideline level, or in a patient-clinician dyad) and support living guidelines.

BACKGROUND As the use of injectable skin fillers increase in popularity, an increase in the reported adverse events is expected. OBJECTIVE This systematic review supports the development of American Society for Dermatologic Surgery practice guideline on the management of adverse events of skin fillers. METHODS AND MATERIALS Several databases for studies on risk factors or treatments of injection-related visual compromise (IRVC), skin necrosis, inflammatory events, and nodules were searched. Meta-analysis was conducted when feasible. RESULTS The review included 182 studies. However, IRVC was very rare (1–2/1,000,000 patients) but had poor prognosis with improvement in 19% of cases. Skin necrosis was more common (approximately 5/1,000) with better prognosis (up to 77% of cases showing improvement). Treatments of IRVC and skin necrosis primarily depend on hyaluronidase injections. Risk of skin necrosis, inflammatory events, and nodules may be lower with certain fillers, brands, injection techniques, and volume. Treatment of inflammatory events and nodules with antibiotics, corticosteroids, 5-FU, and hyaluronidase was associated with high response rate (75%–80%). Most of the studies were small and noncomparative, making the evidence certainty very low. CONCLUSION Practitioners must have adequate knowledge of anatomy, elicit history of skin filler use, and establish preemptive protocols that prepare the clinical practice to manage complications.

AbstractBackground & AimsGlycogenic hepatopathy (GH) in type 1 diabetes‐mellitus (T1DM) is characterized by hepatomegaly and perturbations of liver chemistries (LC) that have not been well studied. Furthermore, misdiagnosis with other hepatic complications of T1DM, such as nonalcoholic fatty liver disease, has been described. We perform a systematic review of biopsy‐proven GH reports in T1DM patients to identify LC patterns.MethodsA systematic review identified reports of biopsy‐proven GH in patients with T1DM. We excluded GH with other liver diseases, Mauriac syndrome, or GH without T1DM. Two reviewers screened and extracted studies and assessed their methodological quality. LC elevation magnitude, AST‐to‐ALT ratio, R‐ratio to designate hepatocellular, cholestatic or mixed pattern of hepatic injury, and evolution of transaminases after glycemic control were analyzed.ResultsA total of 192 patients were included, with median age of 20 years, 73% adults, 66% females, median duration of T1DM before diagnosis 10 years, median adult body mass index 21 kg/m2, median HbA1c 12%, at least one episode of diabetic ketoacidosis 70%, and hepatomegaly 92%. ALT and AST showed moderate‐to‐severe elevation in 78% and 76%, respectively, AST/ALT >1 in 71% and hepatocellular to mixed pattern of hepatic injury in 81%. Transaminase improvement with glycemic control was the rule, regardless of other factors in multilinear regression analysis.ConclusionGH tends to have AST‐predominant elevation with a median of 13 times the upper normal limit and R‐ratio >2, which may distinguish it from other etiologies of AST‐predominant LC elevation, and in the appropriate clinical context, may obviate invasive tests.

CONTEXT: Unplanned PICU readmissions within 48 hours of discharge (to home or a different hospital setting) are considered a quality metric of critical care. OBJECTIVE: We sought to determine identifiable risk factors associated with early unplanned PICU readmissions. DATA SOURCES: A comprehensive search of Medline, Embase, the Cochrane Database of Systematic Reviews, and Scopus was conducted from each database’s inception to July 16, 2018. STUDY SELECTION: Observational studies of early unplanned PICU readmissions (&lt;48 hours) in children (&lt;18 years of age) published in any language were included. DATA EXTRACTION: Two reviewers selected and appraised studies independently and abstracted data. A meta-analysis was performed by using the random-effects model. RESULTS: We included 11 observational studies in which 128 974 children (mean age: 5 years) were evaluated. The presence of complex chronic diseases (odds ratio 2.42; 95% confidence interval 1.06 to 5.55; I2 79.90%) and moderate to severe disability (odds ratio 2.85; 95% confidence interval 2.40 to 3.40; I2 11.20%) had the highest odds of early unplanned PICU readmission. Other significant risk factors included an unplanned index admission, initial admission to a general medical ward, spring season, respiratory diagnoses, and longer initial PICU stay. Readmission was less likely after trauma- and surgery-related index admissions, after direct admission from home, or during the summer season. Modifiable risk factors, such as evening or weekend discharge, revealed no statistically significant association. Included studies were retrospective, which limited our ability to account for all potential confounders and establish causality. CONCLUSIONS: Many risk factors for early unplanned PICU readmission are not modifiable, which brings into question the usefulness of this quality measure.

Abstract Background: Hypercalcemia of malignancy is the second most common cause of hypercalcemia and is associated with significant morbidity and mortality. Several treatment options are available including pharmacological therapy with bisphosphonates, denosumab, glucocorticoids, and calcimimetics, as well as conventional therapy with hydration and possibly calcitonin. While guidelines have previously considered treatment effects, no guideline has yet considered a range of contextual factors impacting recommendations for the management. Objective: The aim of this study is to summarize the available evidence on important decisional factors for the development of guidelines for the treatment of hypercalcemia of malignancy. These include patient’s values and preferences, cost, acceptability, feasibility, and equity. Methods/Design: This is a systematic review of observational studies, case series, trials, reviews and qualitative studies involving treatment of adult patients with hypercalcemia of malignancy. We developed and executed two independent search strategies using five databases: Pubmed, Medline (OVID), Embase.com, CINAHL (EBSCO) and Cochrane, and reviewed their combined output. Two reviewers screened titles and abstracts and full texts and will implement data abstraction from relevant studies independently and in duplicate. The outcomes of interest are the decisional factors that influence drug selection, with possible subgroup analyses by drug class or etiology of hypercalcemia of malignancy. We will present the data collected in a narrative and thematic approach. Discussion: This systematic review will identify important treatment decisional factors, and will assist guidelines panels, physicians and patients to decide on therapeutic options based on the current evidence.

Abstract Background Accurate molecular diagnostic tests are necessary for confirming a diagnosis of coronavirus disease 2019 (COVID-19). Direct detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acids in respiratory tract specimens informs patient, healthcare institution and public health level decision-making. The numbers of available SARS-CoV-2 nucleic acid detection tests are rapidly increasing, as is the COVID-19 diagnostic literature. Thus, the Infectious Diseases Society of America (IDSA) recognized a significant need for frequently updated systematic reviews of the literature to inform evidence-based best practice guidance. Objective The IDSA’s goal was to develop an evidence-based diagnostic guideline to assist clinicians, clinical laboratorians, patients and policymakers in decisions related to the optimal use of SARS-CoV-2 nucleic acid amplification tests. In addition, we provide a conceptual framework for understanding molecular diagnostic test performance, discuss the nuance of test result interpretation in a variety of practice settings and highlight important unmet research needs in the COVID-19 diagnostic testing space. Methods IDSA convened a multidisciplinary panel of infectious diseases clinicians, clinical microbiologists, and experts in systematic literature review to identify and prioritize clinical questions and outcomes related to the use of SARS-CoV-2 molecular diagnostics. Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess the certainty of evidence and make testing recommendations. Results The panel agreed on 17 diagnostic recommendations. Conclusions Universal access to accurate SARS-CoV-2 nucleic acid testing is critical for patient care, hospital infection prevention and the public response to the COVID-19 pandemic. Information on the clinical performance of available tests is rapidly emerging, but the quality of evidence of the current literature is considered moderate to very low. Recognizing these limitations, the IDSA panel weighed available diagnostic evidence and recommends nucleic acid testing for all symptomatic individuals suspected of having COVID-19. In addition, testing is recommended for asymptomatic individuals with known or suspected contact with a COVID-19 case. Testing asymptomatic individuals without known exposure is suggested when the results will impact isolation/quarantine/personal protective equipment (PPE) usage decisions, dictate eligibility for surgery, or inform solid organ or hematopoietic stem cell transplantation timing. Ultimately, prioritization of testing will depend on institutional-specific resources and the needs of different patient populations.